"Speed" Shows More Neurotoxic Effects Than Heroin, Cocaine, or
Alcohol

UPTON, NY --
Two studies by researchers at the U.S. Department of Energy's Brookhaven
National Laboratory provide evidence for the first time that abuse of
methamphetamine ­- the drug commonly known as "speed" -- is
associated with physiological changes in two systems of the human brain.
The changes are evident even for abusers who have not taken the drug for
a year or more. The studies also found that methamphetamine
abusers have reduced cognitive and motor functions, even at one year
after quitting the drug. The findings appear in the March issue of the
American Journal of Psychiatry.

"These
studies provide some of the first clear evidence that methamphetamine at
dose levels taken by human abusers leads to dopamine transporter
reduction," said Brookhaven psychiatrist Nora Volkow, lead
investigator on the study. "For the first time we can also
see that this transporter reduction is associated with motor and
cognitive impairment." Previously, in animal studies and two
small human studies, researchers documented reductions in dopamine
transporters. Past studies did not test whether these reductions
were associated with changes in cognitive and motor function.

"We also
have the first evidence that methamphetamine affects circuits of the
brain other than those regulated by dopamine, and that the drug causes
changes that are consistent with inflammation throughout the
brain," Volkow continued. "This is objective evidence
that methamphetamine is damaging to the brain. These changes are much
greater than what wehave seen with heroin, alcohol, or cocaine. We
need to further study whether these changes are long-lasting and result
in long-term impairment of memory and motor functions, such as motor
speed and motor coordination."

Brain images for (11C)d threo-methylphenidate, which show the
concentration of dopamine transporters in a control and in a
methamphetamine abuser tested 80 days after detoxification. The
abuser shows a much lower concentration than the control. Scale is
at right. Download hi-res
image.

Reduced
Dopamine Transporters, Cognitive and Motor Function

In the first
study, Volkow and colleagues tested both dopamine transporter levels and
motor and cognitive function in 15 detoxified methamphetamine abusers
and 18 control subjects who had not previously used methamphetamine.
Dopamine transporters help transport "used" dopamine, a
neurotransmitter that contributes to feelings of satisfaction and
pleasure, back into the nerve cells that produce it, thus terminating
the pleasure signal.

Each study
volunteer was given an injection called a radiotracer, a radioactive
chemical "tag" designed to bind to dopamine transporters in
the brain. The researchers then scanned the subjects' brains
using a positron emission tomography (PET) camera. The PET camera
picks up the radioactive signal of the tracer and shows where it is
bound to dopamine transporters. The strength of the signal
indicates the number of transporters.

Within two
weeks of the PET scans, the researchers administered a battery of
neuropsychological tests. These included tests of fine and gross
motor function and tests of attention and memory. Methamphetamine abusers
showed a significant reduction in dopamine transporters in the caudate
(27.8%) and putamen (21.1.%) ­ two areas of the striatum, a section of
the brain that controls movement, attention, motivation, and other
higher functions -- compared with non-abusers in the study. The reduction was evident even in abusers who had been detoxified for 11
months or more. Study subjects with reduced dopamine transporters
also exhibited memory impairment and slowed motor function.

Increased
Brain Glucose Metabolism and Inflammation

In the second
study, Volkow's team looked at brain glucose metabolism in order to see
if there was any functional change in regions of the brains of
methamphetamine abusers other than those in which dopamine cells are
active. The same 15 detoxified methamphetamine abusers who
participated in the first study, and 21 non-abusers, received PET scans
following administration of a radioactive tracer. The scans showed
a 14% higher whole brain metabolism in abusers than in non-abusers.
Differences were most accentuated in the parietal cortex ­ an area of
the brain that regulates sensation and coordinates information on space
and spatial relations ­ where abusers showed a 20% higher rate of
metabolism.

"This
finding was a complete surprise," Volkow says. "Most
drug studies have shown decreased metabolism. The increased
metabolism we saw is consistent with an inflammatory response. This result, taken together with our other findings, indicates that this
is a very toxic drug." The presence of inflammation signals
that there is a physical insult to the brain.

Long-Term
Effects

"We
cannot reach any definite conclusions about long-term effects, because
only three of the subjects had been detoxified for an extended period.
But our three primary findings -- dopamine transporter loss, whole
brain inflammation, and loss of motor and cognitive abilities --
document the adverse effects of methamphetamine to the human brain. We
believe more studies must be done to assess if there is long-term damage
from this drug," says Volkow. "We can say unequivocally
that methamphetamine abusers need to be watched by their physicians as
they age to determine whether they begin seeing any effects of
neurodegenerative diseases like Parkinson's." The reduction
in brain dopamine that occurs as these subjects age, in addition to the
loss they experience from use of methamphetamine, may result in symptoms similar to those seen in Parkinson's disease, a severe movement
disorder that results from a loss of dopamine in the brain.

Methamphetamine
is a highly addictive stimulant that dramatically affects the central
nervous system. Long reported as a dominant drug problem in
southern California, methamphetamine abuse has recently become a
substantial problem in other areas of the West and Southwest as well.
Usage has also recently increased in areas of the Midwest and South.
According to a survey by the National Institute on Drug Abuse, an
estimated 4.9 million Americans have tried methamphetamine at some point
in their lives.

Brookhaven scientists have done extensive research on addiction. Studies
by Dr. Volkow and colleagues have shown that dopamine plays an important
role in addiction to cocaine, nicotine, alcohol, heroin, and other
drugs. Previous research at Brookhaven has shown that addictive
drugs increase the level of dopamine in the brain while the subject is
intoxicated, and that addicts have fewer dopamine receptors than
non-addicts.

This study was
funded by the U.S. Department of Energy; the National Institute on Drug
Abuse, part of the National Institutes of Health; the Office of National
Drug Control Policy; and the General Clinical Research Center at
University Hospital Stony Brook. It was done in collaboration with
researchers from the State University of New York at Stony Brook and the
University of California, Los Angeles.

The U.S. Department of Energy's Brookhaven National Laboratory conducts
research in the physical, biomedical, and environmental sciences, as well
as in energy technologies. Brookhaven also builds and operates major
facilities available to university, industrial, and government scientists.
The Laboratory is managed by Brookhaven Science Associates, a limited
liability company founded by Stony Brook University and Battelle, a
nonprofit applied science and technology organization.